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Abstract

Type 2 diabetes mellitus (T2DM) is the most common form of diabetes and accounts for over
90 % of all diabetes cases worldwide. Type 2 diabetes is characterized by insulin resistance
and relative insulin deficiency, either of which may be present at the time that diabetes
becomes clinically manifest. Genetic background was perceived to be linked with the
development of T2DM and its related complications including retinopathy, nephropathy,
diabetic foot and cardiovascular disease. Several variants in the FTO gene were analyzed and
found to be associated with T2DM and obesity in different population. Therefore, our study
was designed to investigate the association of FTO (rs9939609) gene polymorphisms with
T2DM and its related complications.
A case-control study was conducted during the period of 2016-2017. A total of 281 diabetic
patients (181 obese and 15 non-obese) and 118 controls (52 obese and 39 non-obese) were
recruited. All of them were unrelated and aged ≥40 years. The anthropometric, clinical and
biochemical data was collected on a structured questionnaire. The single nucleotide
polymorphism (SNP) in the FTO gene was identified by PCR-RFLP. Comparison of allele
frequencies and genotype distributions between the diabetic and non-diabetic groups were
done using the Pearson‟s Chi-square test. R statistics (v2.8.0). software was used to measure
OR for T2DM adjusted for age, gender and BMI.
Our results showed a strong association between the minor allele A at rs9939609 of the FTOand increase T2DM risk with an allelic odd ratio (OR) of 1.84, (95%CI [1.04-3.05], P=0.034)
after adjustment by age, gender and BMI. Stratified data by glycemic status and across FTO
genotype, revealed a marginally association between the FTO A variant and body mass index
(BMI) in the diabetic group (P=0.057), while no association was found in non-diabetic
control group (P=0.688). Furthermore, no significant association was observed between FTO
genotypes and covariates of age, gender, T2DM complications or any tested metabolic trait in
both diabetic and non-diabetic individuals (P>0.05).
In conclusion, our results demonstrated FTO rs9939609 variant was associated with T2DM.
However, further large-scale study is required to elucidate the role of this variant on the
predisposition of increased BMI in Palestinian population.